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The direction of drilling wells in the plateau slope area is toward finding local favorable water-rich blocks, which are relative groundwater accumulation areas under the control of structure, lithology, and landform. These areas often have obvious geological boundary conditions (such as the presence of a water resisting layer in the vertical direction, the development of a fault fracture zone in the plane), and their corresponding physical boundary often has a relatively low or high resistivity to the surrounding rock. In this paper, the comprehensive geophysical method is used to study the application of water prospecting in the plateau slope of Shuangnuo village, Fuyuan, Yunnan Province. First, according to the hydrogeological conditions (the development of a fault fracture zone and clastic rock is unknown), the plane distribution range and vertical development of the low-resistivity abnormal fault fracture zone are determined using the electrical resistivity tomography (less than 100 m) and audio magnetotelluric methods (100–500 m). Vertically, the development depth and thickness of the clastic rock aquifuge (P 1 l) are determined using the audio frequency magnetotelluric method, which provides a basis for the maximum depth of the borehole layout. The combination of the electrical resistivity tomography and audio frequency magnetotelluric methods can delineate the favorable water-rich block in the study area well and verify that the study area has the prerequisite to become a water prospecting target. To determine the best location of the borehole layout, a combination of the composite profiling, microtremor horizontal-to-vertical spectral ratio (HVSR), apparent resistivity sounding, and K-reflection coefficient methods are carried out in the favorable water-rich block, which delineated by the electrical resistivity tomography and audio frequency magnetotelluric methods. The optimal borehole layout location is determined through the synchronous low resistivity anomaly of the composite profiling method, and the synchronous low resistivity anomaly is determined as a karst fracture zone (qualitative determination) in combination with the HVSR high-value anomaly of the microtremor method. The development depth of the karst fracture zone is finally determined by using the apparent resistivity sounding and K curves. This study reveals that the depth of the drilled hole is 243.5 m, and the water inflow is 144.3 m 3 / day, successfully solving the serious water shortage problem in the local area. The case study results show that the combination of geophysical prospecting methods, namely, the electrical resistivity tomography, audio frequency magnetotelluric, composite profiling, microtremor, apparent resistivity sounding, and k-reflection coefficient methods, is effective for water exploration in the plateau slope zone.

Low-loss photonic integrated circuits and microresonators have enabled a wide range of applications, such as narrow-linewidth lasers and chip-scale frequency combs. To translate these into a widespread technology, attaining ultralow optical losses with established foundry manufacturing is critical. Recent advances in integrated Si 3 N 4 photonics have shown that ultralow-loss, dispersion-engineered microresonators with quality factors Q  > 10 × 10 6 can be attained at die-level throughput. Yet, current fabrication techniques do not have sufficiently high yield and performance for existing and emerging applications, such as integrated travelling-wave parametric amplifiers that require meter-long photonic circuits. Here we demonstrate a fabrication technology that meets all requirements on wafer-level yield, performance and length scale. Photonic microresonators with a mean Q factor exceeding 30 × 10 6 , corresponding to 1.0 dB m −1 optical loss, are obtained over full 4-inch wafers, as determined from a statistical analysis of tens of thousands of optical resonances, and confirmed via cavity ringdown with 19 ns photon storage time. The process operates over large areas with high yield, enabling 1-meter-long spiral waveguides with 2.4 dB m −1 loss in dies of only 5 × 5 mm 2 size. Using a response measurement self-calibrated via the Kerr nonlinearity, we reveal that the intrinsic absorption-limited Q factor of our Si 3 N 4 microresonators can exceed 2 × 10 8 . This absorption loss is sufficiently low such that the Kerr nonlinearity dominates the microresonator’s response even in the audio frequency band. Transferring this Si 3 N 4 technology to commercial foundries can significantly improve the performance and capabilities of integrated photonics. For widespread technological application of nonlinear photonic integrated circuits, ultralow optical losses and high fabrication throughput are required. Here, the authors present a CMOS fabrication technique that realizes integrate photonic microresonators on waver-level with mean quality factors exceeding 30 million and 1 dB/m optical losses.

Thermogenesis is an essential physiological mechanism in both bodies thermal and energy balance. Thermal balance is significantly associated with body heat homeostasis linked thermogenesis-caloric regulation. The caloric or energy balance was reported under facultative thermogenesis within skeletal muscle stimulated by exercise. Importantly, decreased energy expenditure, imbalance energy intake, and loss of energy was developed for types of obesity. Recently, music tempo and frequency are proposed as the new raw model of exercise treatment against the progression of overweight in the population. Thus, our preliminary pre-post test randomized study aimed to investigate the physical-physiological connection between thermogenesis, caloric regulation, acute- maximal and submaximal intensity exercise model and musical frequency/tempo on the body thermal homeostasis and physiological performance in the younger athlete. This study involved 45 participants with homogeneity in age, height, weight, heartbeat, and physical fitness. Interestingly, co-treatment high intensity, moderate intensity exercise and moderate intensity exercise with middle musical tempo/frequency decreased body temperature without relevant alteration on caloric production. Furthermore, this exercise model significantly induced caloric production and energy expenditure in a similar pattern with the placebo. Also, musical-moderate intensity exercise exposure enhanced muscle thermogenesis without effect to overheat condition during the treatment. The circulating level of physiological-physical stress marker (cortisol) significantly decreased post musical exposure. Hence, the development of physical combination therapy for individual onset obesity progress to metabolic syndrome can contribute to the prevention of metabolic disease. This combination model may offer an alternative solution to combating overweight and obesity through musical-exercise co-treatment. However, further studies are emerging to widely establish this model for global communities.

Acoustic isolation and nonreciprocal sound transmission are highly desirable in many practical scenarios. They may be realized with nonlinear or magneto-acoustic effects, but only at the price of high power levels and impractically large volumes. In contrast, nonreciprocal electromagnetic propagation is commonly achieved based on the Zeeman effect, or modal splitting in ferromagnetic atoms induced by a magnetic bias. Here, we introduce the acoustic analog of this phenomenon in a subwavelength meta-atom consisting of a resonant ring cavity biased by a circulating fluid. The resulting angular momentum bias splits the ring's azimuthal resonant modes, producing giant acoustic nonreciprocity in a compact device. We applied this concept to build a linear, magnetic-free circulator for airborne sound waves, observing up to 40-decibel nonreciprocal isolation at audible frequencies.

This paper examines the main approaches and challenges in the design and implementation of underwater wireless sensor networks. We summarize key applications and the main phenomena related to acoustic propagation, and discuss how they affect the design and operation of communication systems and networking protocols at various layers. We also provide an overview of communications hardware, testbeds and simulation tools available to the research community.

A key constraint in genomic testing in oncology is that matched normal specimens are not commonly obtained in clinical practice. Thus, while well-characterized genomic alterations do not require normal tissue for interpretation, a significant number of alterations will be unknown in whether they are germline or somatic, in the absence of a matched normal control. We introduce SGZ (somatic-germline-zygosity), a computational method for predicting somatic vs. germline origin and homozygous vs. heterozygous or sub-clonal state of variants identified from deep massively parallel sequencing (MPS) of cancer specimens. The method does not require a patient matched normal control, enabling broad application in clinical research. SGZ predicts the somatic vs. germline status of each alteration identified by modeling the alteration's allele frequency (AF), taking into account the tumor content, tumor ploidy, and the local copy number. Accuracy of the prediction depends on the depth of sequencing and copy number model fit, which are achieved in our clinical assay by sequencing to high depth (>500x) using MPS, covering 394 cancer-related genes and over 3,500 genome-wide single nucleotide polymorphisms (SNPs). Calls are made using a statistic based on read depth and local variability of SNP AF. To validate the method, we first evaluated performance on samples from 30 lung and colon cancer patients, where we sequenced tumors and matched normal tissue. We examined predictions for 17 somatic hotspot mutations and 20 common germline SNPs in 20,182 clinical cancer specimens. To assess the impact of stromal admixture, we examined three cell lines, which were titrated with their matched normal to six levels (10-75%). Overall, predictions were made in 85% of cases, with 95-99% of variants predicted correctly, a significantly superior performance compared to a basic approach based on AF alone. We then applied the SGZ method to the COSMIC database of known somatic variants in cancer and found >50 that are in fact more likely to be germline.

Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib. J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan. Patients were randomly assigned (1:1) via an interactive web response system using a permuted-block method stratified by Eastern Cooperative Oncology Group performance status, treatment line, and disease stage to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was progression-free survival assessed by an independent review facility. The efficacy analysis was done in the intention-to-treat population, and safety analyses were done in all patients who received at least one dose of the study drug. The study is ongoing and patient recruitment is closed. This study is registered with the Japan Pharmaceutical Information Center (number JapicCTI-132316). Between Nov 18, 2013, and Aug 4, 2015, 207 patients were recruited and assigned to the alectinib (n=103) or crizotinib (n=104) groups. At data cutoff for the second interim analysis, 24 patients in the alectinib group had discontinued treatment compared with 61 in the crizotinib group, mostly due to lack of efficacy or adverse events. At the second interim analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee determined that the primary endpoint of the study had been met (hazard ratio 0·34 [99·7% CI 0·17–0·71], stratified log-rank p<0·0001) and recommended an immediate release of the data. Median progression-free survival had not yet been reached with alectinib (95% CI 20·3–not estimated) and was 10·2 months (8·2–12·0) with crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions due to adverse events were also more prevalent with crizotinib (77 [74%] of 104) than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21 [20%]) than alectinib (nine [9%]) discontinued the study drug because of an adverse event. No adverse events with a fatal outcome occurred in either treatment group. These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer. The dose of alectinib (300 mg twice daily) used in this study is lower than the approved dose in countries other than Japan; however, this limitation is being addressed in the ongoing ALEX study. Chugai Pharmaceutical Co, Ltd.

Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers’ compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering.

In the pursuit of implementing safety monitoring within Industry 4.0 smart production, deep learning methodologies are employed to harness the audio signals emanating from the operation of machinery and equipment, facilitating anomaly detection. Aiming to address the challenge of the few-shot samples for anomalous sound detection in an unsupervised setting, this paper introduces a machine anomalous sound detection method using an Audio Synthesis Adversarial Generative Network (ASGAN). The augmentation of classifiers within the network’s discriminator is proposed to execute a multi-classification task, thereby transforming the unsupervised training milieu into a semi-supervised one and enhancing the discriminator’s accuracy. To address the oversight of audio frequency domain features by conventional generative adversarial networks, the squeeze-and-excitation network is applied to concentrate on crucial frequency bands within the frequency domain. Experimental validation is conducted by using the DCASE Challenge Task2 dataset, revealing that the performance of the anomaly detection method leveraging audio synthesis generative adversarial networks surpasses that of the baseline system.

Domestication and the subsequent selection of animals for either economic or morphological features can leave a variety of imprints on the genome of a population. Genomic regions subjected to high selective pressures often show reduced genetic diversity and frequent runs of homozygosity (ROH). Therefore, the objective of the present study was to use 42,182 autosomal SNPs to identify genomic regions in 3,191 sheep from six commercial breeds subjected to selection pressure and to quantify the genetic diversity within each breed using ROH. In addition, the historical effective population size of each breed was also estimated and, in conjunction with ROH, was used to elucidate the demographic history of the six breeds. ROH were common in the autosomes of animals in the present study, but the observed breed differences in patterns of ROH length and burden suggested differences in breed effective population size and recent management. ROH provided a sufficient predictor of the pedigree inbreeding coefficient, with an estimated correlation between both measures of 0.62. Genomic regions under putative selection were identified using two complementary algorithms; the fixation index and hapFLK. The identified regions under putative selection included candidate genes associated with skin pigmentation, body size and muscle formation; such characteristics are often sought after in modern-day breeding programs. These regions of selection frequently overlapped with high ROH regions both within and across breeds. Multiple yet uncharacterised genes also resided within putative regions of selection. This further substantiates the need for a more comprehensive annotation of the sheep genome as these uncharacterised genes may contribute to traits of interest in the animal sciences. Despite this, the regions identified as under putative selection in the current study provide an insight into the mechanisms leading to breed differentiation and genetic variation in meat production.